The Incidence of Breast Cancer Recurrence 10-32 Years After Primary Diagnosis

Abstract

Background: Extended, more effective breast cancer treatments have increased the prevalence of long-term survivors. We investigated the risk of late breast cancer recurrence (BCR), 10 years or more after primary diagnosis, and associations between patient and tumor characteristics at primary diagnosis and late BCR up to 32 years after primary breast cancer diagnosis.

Methods: Using the Danish Breast Cancer Group clinical database, we identified all women with an incident early breast cancer diagnosed during 1987-2004. We restricted to women who survived 10 years without a recurrence or second cancer (10-year disease-free survivors) and followed them from 10 years after breast cancer diagnosis date until late recurrence, death, emigration, second cancer, or December 31, 2018. We calculated incidence rates per 1000 person-years and cumulative incidences for late BCR, stratifying by patient and tumor characteristics. Using Cox regression, we calculated adjusted hazard ratios for late BCR accounting for competing risks.

Results: Among 36 924 women with breast cancer, 20 315 became 10-year disease-free survivors. Of these, 2595 developed late BCR (incidence rate = 15.53 per 1000 person-years, 95% confidence interval = 14.94 to 16.14; cumulative incidence = 16.6%, 95% confidence interval = 15.8% to 17.5%) from year 10 to 32 after primary diagnosis. Tumor size larger than 20 mm, lymph node-positive disease, and estrogen receptor-positive tumors were associated with increased cumulative incidences and hazards for late BCR.

Conclusions: Recurrences continued to occur up to 32 years after primary diagnosis. Women with high lymph node burden, large tumor size, and estrogen receptor-positive tumors had increased risk of late recurrence. Such patients may warrant extended surveillance, more aggressive treatment, or new therapy approaches.

Figure 1.

The cumulative incidence of late breast cancer recurrence among women diagnosed with early-stage breast cancer between 1987 and 2004, alive and without a recurrence or second cancer 10 years after primary diagnosis.

Figure 2.

Cumulative incidences of late breast cancer recurrence among 20 315 women diagnosed with early-stage breast cancer in Denmark, 1987-2004, alive and without a recurrence or second cancer 10 years after primary diagnosis, stratified according to: A) T1 tumors (tumor diameter ≤2.0 cm) and nodal status (N0, no nodes; N1-3, 1-3 nodes; N4-9, 4-9 nodes); B) T2 tumors (tumor diameter, >2.0-5.0 cm) and nodal status (N0, no nodes; N1-3, 1-3 nodes; N4-9, 4-9 nodes); C) malignancy grade (grade I, II, III, or not graded); D) tumor size (≤20 or >20 mm); E) lymph node status (N0, N1-3, N ≥ 4); F) estrogen receptor status (negative, positive, or unknown); and G) type of primary surgery (mastectomy + RT, mastectomy, or BCS + RT) ^aNo confidence intervals are shown due to close lines. ^bThe unknown category is not shown. BCS = breast-conserving surgery; RT = radiation therapy.

Figure 3.

Hazard ratios (HRs) for late breast cancer recurrence, according to clinico-pathological factors at baseline, among 20 315 women diagnosed with early-stage breast cancer in Denmark, 1987-2004, alive and without a recurrence or second cancer 10 years after primary diagnosis. Adjusted for age, calendar period for primary tumor, menopausal status, Charlson Comorbidity Index (CCI; 10 years after primary diagnosis), stage, grade, estrogen receptor status, endocrine therapy, type of primary surgery, and chemotherapy except for the one actually examined. When we examined lymph node status, we did not adjust for stage but adjusted for tumor size; when we examined tumor size, we did not adjust for stage but lymph node status; and when we examined stage, we did not adjust for lymph node status and tumor size. Error bars represent the 95% confidence intervals (CI). ^aThe unknown category is not shown. BCS = breast-conserving surgery; RT = radiation therapy.